Gut microbiota and diabetes: from pathogenesis to therapeutic perspective

More than several hundreds of millions of people will be diabetic and obese over the next decades in front of which the actual therapeutic approaches aim at treating the consequences rather than causes of the impaired metabolism. This strategy is not efficient and new paradigms should be found. The wide analysis of the genome cannot predict or explain more than 10–20% of the disease, whereas changes in feeding and social behavior have certainly a major impact. However, the molecular mechanisms linking environmental factors and genetic susceptibility were so far not envisioned until the recent discovery of a hidden source of genomic diversity, i.e., the metagenome. More than 3 million genes from several hundreds of species constitute our intestinal microbiome. First key experiments have demonstrated that this biome can by itself transfer metabolic disease. The mechanisms are unknown but could be involved in the modulation of energy harvesting capacity by the host as well as the low-grade inflammation and the corresponding immune response on adipose tissue plasticity, hepatic steatosis, insulin resistance and even the secondary cardiovascular events. Secreted bacterial factors reach the circulating blood, and even full bacteria from intestinal microbiota can reach tissues where inflammation is triggered. The last 5 years have demonstrated that intestinal microbiota, at its molecular level, is a causal factor early in the development of the diseases. Nonetheless, much more need to be uncovered in order to identify first, new predictive biomarkers so that preventive strategies based on pre- and probiotics, and second, new therapeutic strategies against the cause rather than the consequence of hyperglycemia and body weight gain

Development of a Seating Comfort Questionnaire for Motorcycles

Objective The aim of this study is to develop a reliable and valid Motorcycle Seating Comfort Questionnaire (MSCQ). Background Motorcycle seat development is an iterative process based on subjective evaluations; however, there are no established subjective tools for evaluation of seating comfort. Research also suggests that seating comfort in motorcycles is poor and needs improvement. The development of a MSCQ therefore is an important step that can enable further research and aid in improving the design of motorcycle seats. Method The MSCQ is developed following guidelines available in literature and referring to established questionnaires for seating comfort in passenger cars. The MSCQ is further refined based on pilot studies and interviews with experts. The final version of the MSCQ is then statistically evaluated for reliability and validity. The reliability is evaluated using a test-retest protocol with 31 volunteers. The validity is evaluated by comparing the ratings of the MSCQ with that of the Category Partitioning Scale (CP50 scale). The validity test is carried out with 15 volunteers evaluating five motorcycles using both scales. Results The results show that the MSCQ is reliable with a significant test-retest reliability coefficient (r = 0.72, p < .01, n = 31) and internal consistency (Cronbach's = 0.81, n = 31). The results also show that ratings of the MSCQ have a significant correlation (r = -0.765, p < .05, n = 15) with that of CP50, establishing its validity. Conclusions A Motorcycle Seating Comfort Questionnaire is developed in this study with statistically established reliability and validity. Applications The MSCQ can be used as a tool for evaluation of seating comfort in motorcycles. The MSCQ can also form a basis for further research on motorcycle seating to develop prediction models and guidelines for the design of motorcycle seats

Nucleobase-Modified Triplex-Forming Peptide Nucleic Acids for Sequence-Specific Recognition of Double-Stranded RNA

Because of the important roles noncoding RNAs play in gene expression, their sequence-specific recognition is important for both fundamental science and the pharmaceutical industry. However, most noncoding RNAs fold in complex helical structures that are challenging problems for molecular recognition. Herein, we describe a method for sequence-specific recognition of double-stranded RNA using peptide nucleic acids (PNAs) that form triple helices in the major grove of RNA under physiologically relevant conditions. We also outline methods for solid-phase conjugation of PNA with cell-penetrating peptides and fluorescent dyes. Protocols for PNA preparation and binding studies using isothermal titration calorimetry are described in detail